IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-021-27639-0.html
   My bibliography  Save this article

Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling

Author

Listed:
  • Jana Zecha

    (Technical University of Munich (TUM)
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
    Dynamic Omics, Centre for Genomics Research, Discovery Sciences, R&D AstraZeneca)

  • Wassim Gabriel

    (Technical University of Munich (TUM)
    Technical University of Munich (TUM))

  • Ria Spallek

    (Klinikum rechts der Isar, TUM
    TranslaTUM, Center for Translational Cancer Research, TUM)

  • Yun-Chien Chang

    (Technical University of Munich (TUM))

  • Julia Mergner

    (Technical University of Munich (TUM)
    Bavarian Biomolecular Mass Spectrometry Center at Klinikum rechts der Isar (BayBioMS@MRI), TUM)

  • Mathias Wilhelm

    (Technical University of Munich (TUM)
    Technical University of Munich (TUM))

  • Florian Bassermann

    (German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
    Klinikum rechts der Isar, TUM
    TranslaTUM, Center for Translational Cancer Research, TUM)

  • Bernhard Kuster

    (Technical University of Munich (TUM)
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
    Bavarian Biomolecular Mass Spectrometry Center (BayBioMS), TUM)

Abstract

Proteome-wide measurements of protein turnover have largely ignored the impact of post-translational modifications (PTMs). To address this gap, we employ stable isotope labeling and mass spectrometry to measure the turnover of >120,000 peptidoforms including >33,000 phosphorylated, acetylated, and ubiquitinated peptides for >9,000 native proteins. This site-resolved protein turnover (SPOT) profiling discloses global and site-specific differences in turnover associated with the presence or absence of PTMs. While causal relationships may not always be immediately apparent, we speculate that PTMs with diverging turnover may distinguish states of differential protein stability, structure, localization, enzymatic activity, or protein-protein interactions. We show examples of how the turnover data may give insights into unknown functions of PTMs and provide a freely accessible online tool that allows interrogation and visualisation of all turnover data. The SPOT methodology is applicable to many cell types and modifications, offering the potential to prioritize PTMs for future functional investigations.

Suggested Citation

  • Jana Zecha & Wassim Gabriel & Ria Spallek & Yun-Chien Chang & Julia Mergner & Mathias Wilhelm & Florian Bassermann & Bernhard Kuster, 2022. "Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27639-0
    DOI: 10.1038/s41467-021-27639-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27639-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27639-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Matthias Selbach & Björn Schwanhäusser & Nadine Thierfelder & Zhuo Fang & Raya Khanin & Nikolaus Rajewsky, 2008. "Widespread changes in protein synthesis induced by microRNAs," Nature, Nature, vol. 455(7209), pages 58-63, September.
    2. Toby Mathieson & Holger Franken & Jan Kosinski & Nils Kurzawa & Nico Zinn & Gavain Sweetman & Daniel Poeckel & Vikram S. Ratnu & Maike Schramm & Isabelle Becher & Michael Steidel & Kyung-Min Noh & Gio, 2018. "Systematic analysis of protein turnover in primary cells," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    3. Eugenio F. Fornasiero & Sunit Mandad & Hanna Wildhagen & Mihai Alevra & Burkhard Rammner & Sarva Keihani & Felipe Opazo & Inga Urban & Till Ischebeck & M. Sadman Sakib & Maryam K. Fard & Koray Kirli &, 2018. "Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    4. J. Wade Harper & Eric J. Bennett, 2016. "Proteome complexity and the forces that drive proteome imbalance," Nature, Nature, vol. 537(7620), pages 328-338, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Feng Yuan & Yi Li & Xinyue Zhou & Peiyuan Meng & Peng Zou, 2023. "Spatially resolved mapping of proteome turnover dynamics with subcellular precision," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Ji Min Lee & Henrik M. Hammarén & Mikhail M. Savitski & Sung Hee Baek, 2023. "Control of protein stability by post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Simone Sanzo & Katrin Spengler & Anja Leheis & Joanna M. Kirkpatrick & Theresa L. Rändler & Tim Baldensperger & Therese Dau & Christian Henning & Luca Parca & Christian Marx & Zhao-Qi Wang & Marcus A., 2021. "Mapping protein carboxymethylation sites provides insights into their role in proteostasis and cell proliferation," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    4. Henrik M. Hammarén & Eva-Maria Geissen & Clement M. Potel & Martin Beck & Mikhail M. Savitski, 2022. "Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. W.L. Bai & Y.L. Dang & R.H. Yin & R.L. Yin & W.Q. Jiang & Z.Y. Wang & Y.B. Zhu & J.J. Wang & Z.H. Zhao & G.B. Luo, 2016. "Combination of let-7d-5p, miR-26a-5p, and miR-15a-5p is suitable normalizer for studying microRNA expression in skin tissue of Liaoning cashmere goat during hair follicle cycle," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 61(3), pages 99-107.
    6. Tal M. Dankovich & Rahul Kaushik & Linda H. M. Olsthoorn & Gabriel Cassinelli Petersen & Philipp Emanuel Giro & Verena Kluever & Paola Agüi-Gonzalez & Katharina Grewe & Guobin Bao & Sabine Beuermann &, 2021. "Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R," Nature Communications, Nature, vol. 12(1), pages 1-23, December.
    7. Claudia M. Fusco & Kristina Desch & Aline R. Dörrbaum & Mantian Wang & Anja Staab & Ivy C. W. Chan & Eleanor Vail & Veronica Villeri & Julian D. Langer & Erin M. Schuman, 2021. "Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    8. Peng Wang & Shangwei Ning & Qianghu Wang & Ronghong Li & Jingrun Ye & Zuxianglan Zhao & Yan Li & Teng Huang & Xia Li, 2013. "mirTarPri: Improved Prioritization of MicroRNA Targets through Incorporation of Functional Genomics Data," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-12, January.
    9. Ramkrishna Mitra & Sanghamitra Bandyopadhyay, 2011. "MultiMiTar: A Novel Multi Objective Optimization based miRNA-Target Prediction Method," PLOS ONE, Public Library of Science, vol. 6(9), pages 1-13, September.
    10. Alessandra Stangherlin & Joseph L. Watson & David C. S. Wong & Silvia Barbiero & Aiwei Zeng & Estere Seinkmane & Sew Peak Chew & Andrew D. Beale & Edward A. Hayter & Alina Guna & Alison J. Inglis & Ma, 2021. "Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    11. Xu Wu & Bogdana Borca & Suman Sen & Sebastian Koslowski & Sabine Abb & Daniel Pablo Rosenblatt & Aurelio Gallardo & Jesús I. Mendieta-Moreno & Matyas Nachtigall & Pavel Jelinek & Stephan Rauschenbach , 2023. "Molecular sensitised probe for amino acid recognition within peptide sequences," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    12. Daniel P. Bondeson & Zachary Mullin-Bernstein & Sydney Oliver & Thomas A. Skipper & Thomas C. Atack & Nolan Bick & Meilani Ching & Andrew A. Guirguis & Jason Kwon & Carly Langan & Dylan Millson & Bren, 2022. "Systematic profiling of conditional degron tag technologies for target validation studies," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    13. Ray M Marín & Jiří Vaníček, 2012. "Optimal Use of Conservation and Accessibility Filters in MicroRNA Target Prediction," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-11, February.
    14. Thao Nguyen & Eli J. Costa & Tim Deibert & Jose Reyes & Felix C. Keber & Miroslav Tomschik & Michael Stadlmeier & Meera Gupta & Chirag K. Kumar & Edward R. Cruz & Amanda Amodeo & Jesse C. Gatlin & Mar, 2022. "Differential nuclear import sets the timing of protein access to the embryonic genome," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    15. Prateek Kumar & Annie M. Goettemoeller & Claudia Espinosa-Garcia & Brendan R. Tobin & Ali Tfaily & Ruth S. Nelson & Aditya Natu & Eric B. Dammer & Juliet V. Santiago & Sneha Malepati & Lihong Cheng & , 2024. "Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer’s pathology," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    16. David Lyon & Maria Angeles Castillejo & Christiana Staudinger & Wolfram Weckwerth & Stefanie Wienkoop & Volker Egelhofer, 2014. "Automated Protein Turnover Calculations from 15N Partial Metabolic Labeling LC/MS Shotgun Proteomics Data," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-10, April.
    17. Roman Vetter & Dagmar Iber, 2022. "Precision of morphogen gradients in neural tube development," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    18. Alicia Hurtado & Irene Mota-Gómez & Miguel Lao & Francisca M. Real & Johanna Jedamzick & Miguel Burgos & Darío G. Lupiáñez & Rafael Jiménez & Francisco J. Barrionuevo, 2024. "Complete male-to-female sex reversal in XY mice lacking the miR-17~92 cluster," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    19. Adam A Margolin & Shao-En Ong & Monica Schenone & Robert Gould & Stuart L Schreiber & Steven A Carr & Todd R Golub, 2009. "Empirical Bayes Analysis of Quantitative Proteomics Experiments," PLOS ONE, Public Library of Science, vol. 4(10), pages 1-15, October.
    20. Chikako Ragan & Michael Zuker & Mark A Ragan, 2011. "Quantitative Prediction of miRNA-mRNA Interaction Based on Equilibrium Concentrations," PLOS Computational Biology, Public Library of Science, vol. 7(2), pages 1-11, February.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27639-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.